Morpho-Genomic Deep Learning for Ovarian Cancer Subtype and Gene Mutation Prediction from Histopathology
This work addresses the need for cost-effective precision oncology in ovarian cancer diagnosis by enabling genomic prediction from standard histopathology, though it is incremental as it builds on existing deep learning methods.
This study tackled the problem of predicting ovarian cancer subtypes and gene mutations from histopathology images by developing a hybrid deep learning pipeline that integrates nuclear morphometry and deep image features, achieving an overall subtype classification accuracy of 84.2% and moderate-to-high AUC scores for gene mutation inference (e.g., 0.82 for TP53).
Ovarian cancer remains one of the most lethal gynecological malignancies, largely due to late diagnosis and extensive heterogeneity across subtypes. Current diagnostic methods are limited in their ability to reveal underlying genomic variations essential for precision oncology. This study introduces a novel hybrid deep learning pipeline that integrates quantitative nuclear morphometry with deep convolutional image features to perform ovarian cancer subtype classification and gene mutation inference directly from Hematoxylin and Eosin (H&E) histopathological images. Using $\sim45,000$ image patches sourced from The Cancer Genome Atlas (TCGA) and public datasets, a fusion model combining a ResNet-50 Convolutional Neural Network (CNN) encoder and a Vision Transformer (ViT) was developed. This model successfully captured both local morphological texture and global tissue context. The pipeline achieved a robust overall subtype classification accuracy of $84.2\%$ (Macro AUC of $0.87 \pm 0.03$). Crucially, the model demonstrated the capacity for gene mutation inference with moderate-to-high accuracy: $AUC_{TP53} = 0.82 \pm 0.02$, $AUC_{BRCA1} = 0.76 \pm 0.04$, and $AUC_{ARID1A} = 0.73 \pm 0.05$. Feature importance analysis established direct quantitative links, revealing that nuclear solidity and eccentricity were the dominant predictors for TP53 mutation. These findings validate that quantifiable histological phenotypes encode measurable genomic signals, paving the way for cost-effective, precision histopathology in ovarian cancer triage and diagnosis.